Ammonium Chloride → (3S,5R)-3-((E)-but-2-enyl)-5-(4-fluorophenyl)dihydrofuran-2(3H)-one

Temperature

-70 °C

To the solution of lithium bis(trimethylsilyl)amide (2.4 mL, 2.4 mmol, 1M in THF) in anhydrous 20 mL THF at −70° C. was slowly added over 15 minutes (R)-5-(4-fluorophenyl)dihydrofuran-2(3H)-one (360 mg, 2.0 mmol) as a solution in 1.0 mL THF. The reaction mixture was stirred for 20 min at −70° C. and then for 10 min at room temperature. The mixture was cooled to −70° C. and to it was slowly added a pre-cooled solution of 1-bromo-but-2-ene (324 mg, 2.4 mmol) in 400 μl HMPA an 100 μL of THF. The resulting mixture was stirred at −70° C. for 2 h and the temperature was slowly raised over a period of 2 h. The mixture was poured into 20 mL saturated NH4Cl and extracted with ethyl acetate (3×30 mL). The combined organic layers were washed with brine (2×20 mL) and dried over Na2SO4. The solvent was removed under reduced pressure and the product isolated by Flash column chromatography eluting with 0% to 50% ethyl acetate/hexane to the title compound.

1. waitfor 10 min at room temperature
2. temperatureThe mixture was cooled to −70° C. and to it
3. stirringThe resulting mixture was stirred at −70° C. for 2 h
4. temperaturethe temperature was slowly raised over a period of 2 h
5. extractionextracted with ethyl acetate (3×30 mL)
6. washThe combined organic layers were washed with brine (2×20 mL)
7. dry with materialdried over Na2SO4
8. customThe solvent was removed under reduced pressure
9. customthe product isolated by Flash column chromatography
10. washeluting with 0% to 50% ethyl acetate/hexane to the title compound

ORD record

ord-7bbb1d34b20f4b35a164b20c51ecf1f0

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08119692B2